title: Systematic profiling of Caenorhabditis elegans locomotive behaviors reveals additional components in G-protein Gαq signaling.
abstract: Genetic screens have been widely applied to uncover genetic mechanisms of movement disorders. However, most screens rely on human observations of qualitative differences. Here we demonstrate the application of an automatic imaging system to conduct a quantitative screen for genes regulating the locomotive behavior in Caenorhabditis elegans. Two hundred twenty-seven neuronal signaling genes with viable homozygous mutants were selected for this study. We tracked and recorded each animal for 4 min and analyzed over 4,400 animals of 239 genotypes to obtain a quantitative, 10-parameter behavioral profile for each genotype. We discovered 87 genes whose inactivation causes movement defects, including 50 genes that had never been associated with locomotive defects. Computational analysis of the high-content behavioral profiles predicted 370 genetic interactions among these genes. Network partition revealed several functional modules regulating locomotive behaviors, including sensory genes that detect environmental conditions, genes that function in multiple types of excitable cells, and genes in the signaling pathway of the G protein Gαq, a protein that is essential for animal life and behavior. We developed quantitative epistasis analysis methods to analyze the locomotive profiles and validated the prediction of the γ isoform of phospholipase C as a component in the Gαq pathway. These results provided a system-level understanding of how neuronal signaling genes coordinate locomotive behaviors. This study also demonstrated the power of quantitative approaches in genetic studies.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Boanerges
authors.initials: B
authors.lastname: Aleman-Meza
authors.forename: Shahla
authors.initials: S
authors.lastname: Gharib
authors.forename: Marta K
authors.initials: MK
authors.lastname: Labocha
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Cronin
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhong
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D004843:Epistasis, Genetic / Q000235:genetics / Q000502:physiology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D008124:Locomotion / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: gene network; high-content screening; locomotion